Effect and significance of tetrandrine on expression of Rho/Rho kinase in fetal lung of congenital diaphragmatic hernia rats / 重庆医学

ABSTRACT

Objective To investigate the effect and significance of the traditional Chinese medicine tetrandrine(TET) prenatal intervention on the expression of RhoA protein and Rho kinase ROCK1 in the fetal lung of congenital diaphragmatic hernia (CDH) rat model.Methods SD female rats with 9.5 d of gestation were randomly divided into the control group,CDH group and TET group.The CDH group and TET intervention group were administered with nitrofen by gavage for establishing CDH model.The TET intervention was given on 16.5 d of gestation.The fetal rat lungs were taken by cesarean section on 21.5 d of gestation and the lung weight/body ratio(Lw/Bw) was measured.The lung development and small pulmonary arterial morphologic changes in HE staining in all groups were observed with microscopy.The protein expression of RhoA and Rho kinase ROCK1were respectively examined by immunohistochemistry and Western blot.Results In the CDH group,the lungs had obvious maldevelopment and the fetal lung development in the TET group was close to that in the control group.The lung development indicators of Lw/Bw,PAA％,and lung vascular remodeling indicators of lumen area and vascular total area ratio(LA％) in the CDH group were significantly lower than those in the control group(2.11±0.36 vs.4.24±0.31;33.60±3.12 vs.58.81 ±2.92;38.58±2.15 vs.61.20±3.23,P＜0.05),the indicators of Lw/Bw.PAA％ and LA％ after TET intervention were significantly improved compared with the CDH group(3.61±0.24 vs.2.11±0.36;42.46±3.68 vs.33.60±3.12;56.07±3.32 vs.38.58±2.15,all P ＜0.05);the ratio of small pulmonary artery wall thickness to vascular external diameter (WT％) and the medium thickness percentage (MT％) in CDH group were significantly higher than those in the control group(26.64±2.41 vs.13.50±1.45 and 25.98±2.79 vs.16.47±2.07,P＜0.05),WT％ and MT％ in the TET group were obviously lower than those in the CDH group (16.02±2.35 vs.26.64± 2.41 and 17.96 ± 1.95 vs.25.98 ± 2.79,P＜0.05).The immunohistochemistry and Western blot detection indicated that the expressions of RhoA and ROCK1 from low to high were the control group ＜TET group ＜ CDH group.Conclusion Pulmonary hypoplasia and lung vascular remodeling exist in fetal rats with CDH and Rho/Rho kinase signaling pathway may be involved in the process.Prenatally giving TET may play the lung protective effect by regulating the Rho/Rho signal pathway.